NM_000213.5(ITGB4):c.178C>T (p.Arg60Cys) AND not provided

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jan 19, 2024
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV003560024.2

Allele description [Variation Report for NM_000213.5(ITGB4):c.178C>T (p.Arg60Cys)]

NM_000213.5(ITGB4):c.178C>T (p.Arg60Cys)

Gene:

ITGB4:integrin subunit beta 4 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

17q25.1

Genomic location:

Preferred name:

NM_000213.5(ITGB4):c.178C>T (p.Arg60Cys)

HGVS:

NC_000017.11:g.75727419C>T
NG_007372.1:g.10985C>T
NG_007372.2:g.10962C>T
NM_000213.5:c.178C>TMANE SELECT
NM_001005619.1:c.178C>T
NM_001005731.3:c.178C>T
NM_001321123.2:c.178C>T
NP_000204.3:p.Arg60Cys
NP_001005619.1:p.Arg60Cys
NP_001005731.1:p.Arg60Cys
NP_001308052.1:p.Arg60Cys
NC_000017.10:g.73723500C>T

Protein change:

R60C

Molecular consequence:

NM_000213.5:c.178C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001005619.1:c.178C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001005731.3:c.178C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001321123.2:c.178C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004297534	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 19, 2024)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 16473856, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004297534

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 19, 2024)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Epidermolysis bullosa. I. Molecular genetics of the junctional and hemidesmosomal variants.

Varki R, Sadowski S, Pfendner E, Uitto J.

J Med Genet. 2006 Aug;43(8):641-52. Epub 2006 Feb 10.

PubMed [citation]

PMID:: 16473856
PMCID:: PMC2564586

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group, Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004297534.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 60 of the ITGB4 protein (p.Arg60Cys). This variant is present in population databases (no rsID available, gnomAD 0.004%). This missense change has been observed in individual(s) with epidermolysis bullosa (PMID: 16473856). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt ITGB4 protein function with a negative predictive value of 80%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

ClinVar

Relating variation to medicine